Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients

Abstract

Background: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule.

Methods: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses.

Results: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion.

Conclusions: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

Keywords: melanoma lymphatic drainage; melanoma sentinel lymph nodes; tilmanocept (lymphoseek).

Figure 1.

Cutaneous melanoma lymphatic drainage. Graphical depiction of hypothetical lymphatic drainage patterns from cutaneous melanoma to downstream lymph nodes. (A) Primary lesion drains first to a single SLN and then to additional nodes downstream (single channel, multiple nodes). (B, C) Cutaneous melanoma drains to several nodes through independent pathways (parallel channels, multiple nodes).

Figure 2.

Preoperative lymphoscintigraphy: Patient illustration. Patient is a 32-year-old Caucasian who presented with an irregular mole on the upper midline back at T6/T7. On 05/28/2013, biopsy revealed .6-mm thick melanoma, Clark level II, non-ulcerated with one mitosis per square millimeter. Subsequently, the patient underwent a wide local re-excision followed by SLN mapping with Technetium-99m-labeled Tilmanocept and selective SLN biopsy. Preoperatively, four intradermal injections of Technetium-99m-labeled Tilmanocept were performed surrounding the primary site on the back. Standard preoperative planar SLN lymphoscintigraphy revealed expected intense activity at the injection site with multiple visualized channels extending bilaterally to the axillae (A, posterior; B, anterior, flow images). SPECT was performed with low-dose CT for attenuation correction of the SPECT data and anatomic correlation (C, axial SPECT/CT; D, coronal volumetric SPECT/CT). Preoperative mapping demonstrated one and two foci of radiotracer accumulation in the left and right axilla, respectively. Intraoperatively, three and four SLNs were biopsied from the left and right axilla, respectively. On pathological assessment, a single left-sided axillary lymph node was positive for a subcapsular deposit of metastatic melanoma measuring at least .3-mm in diameter (E-F, representative 20x images of anti-Melan A and anti-S100 immunohistochemical stains of the subcapsular micrometastasis, respectively).

Figure 3.

Distribution of Number of Sentinel Nodes Harvested (Top) Number of SLN3 harvested (x-axis) plotted alongside frequency of patients (y-axis) in the studied population; (Bottom) Tabular format of data.